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Summary: Background: School-based targeted preventive chemotherapy (PC), the primary strategy for soil-transmitted helminth (STH) control, typically focusing on primary schoolchildren, was expanded to secondary school students in the Philippines in 2016. This program still excludes adults, who may also suffer from considerable morbidity and can be a significant reservoir of infection. Mass drug administration (MDA), where the entire population is treated, would bring additional health benefits but will also increase implementation costs. The incremental cost of implementing MDA for STH control compared to expanded school-based targeted PC, however, is unknown. Methods: A cost survey was conducted in Zamboanga Peninsula region in 2021 to estimate the economic and financial cost of implementing MDA compared to the expanded school-based targeted PC from a government payer perspective. A budget impact analysis was conducted to estimate the financial cost to the government of implementing MDA over a five-year timeframe. Monte Carlo simulation accounted for uncertainty in cost estimates. Costs were reported in 2021 United States Dollars ($). Findings: The economic cost of MDA was $809,000 per year (95% CI: $679,000–$950,000) or $0.22 per person targeted (95% CI: $0.19–$0.26), while the expanded school-based targeted PC would cost $625,000 (95% CI: $549,000–$706,000) or $0.57 per person targeted (95% CI: $0.50–$0.64). Over five years, the financial cost to the government for MDA would be $3,113,000 (95% CI: $2,475,000–$3,810,000); $740,000 (95% CI: $486,000–$1,019,000) higher than expanded school-based targeted PC. Interpretation: Implementing MDA in the region will increase the economic and financial costs by 29% and 31%, respectively, when compared to expanded school-based targeted PC. Implementing MDA would require the Department of Health to increase their total expenditure for STH control by 0.2% and could be key in addressing the ongoing STH burden. Funding: The project was funded by the Australian Centre for the Control and Elimination of Neglected Tropical Diseases (NHMRC GA19028), and JPCDT was supported by a UNSW Scientia PhD Scholarship. SVN is funded by an NHMRC Investigator Grant (APP 2018220).

Abstract Background Soil transmitted helminth (STH) infections are estimated to impact 24% of the world’s population and are responsible for chronic and debilitating morbidity. Disadvantaged communities are among the worst affected and are further marginalized as infection prevalence fuels the poverty cycle. Ambitious targets have been set to eliminate STH infections, but accurate epidemiological data will be required to inform appropriate interventions. This paper details the protocol for an analysis that aims to produce spatial prediction mapping of STH prevalence in the Western Pacific Region (WPR). Methods The protocol follows the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocol (PRISMA-P) guidelines. The study design will combine the principles of systematic review, meta-analysis, and geospatial analysis. Systematic searches will be undertaken in PubMed, Scopus, ProQuest, Embase, and Web of Science for studies undertaken post 2000, to identify surveys that enable the prevalence of human STH infection within the WPR to be calculated. Covariate data for multivariable analysis will be obtained from publicly accessible sources. Survey data will be geolocated, and STH prevalence and covariates will be linked to produce a spatially referenced dataset for analysis. Bayesian model-based geostatistics will be used to generate spatially continuous estimates of STH prevalence mapped to a resolution of 1 km2. A separate geospatial model will be constructed for each STH species. Predictions of prevalence will be made for unsampled locations and maps will be overlaid for each STH species to obtain co-endemicity maps. Discussion This protocol facilitates study replication and may be applied to other infectious diseases or alternate geographies. Results of the subsequent analysis will identify geographies with high STH prevalence’s and can be used to inform resource allocation in combating this neglected tropical disease. Trial registration Open Science Framework: osf.io/qmxcj.

Abstract Background Current soil-transmitted helminth (STH) control guidelines endorse the use of albendazole or mebendazole for school-based targeted preventive chemotherapy (PC), yet their reduced efficacy against Strongyloides stercoralis and Trichuris trichiura presents significant limitations. Emerging evidence indicates that community-wide PC [or mass drug administration (MDA)] using ivermectin, commonly used in other neglected tropical disease (NTD) control programs, may play an important role in controlling these parasites. We conducted a systematic review and meta-analysis to evaluate the effectiveness of ivermectin PC in reducing STH prevalence in endemic populations. Methods We searched Pubmed, EMBASE, and Web of Science on February 14, 2023, for studies that investigated the effectiveness of ivermectin PC, either alone or in combination with other anthelmintic drugs, on STH infections, and provided a measure of STH prevalence before and after PC. We calculated pooled prevalence reductions for each STH using random-effects meta-analyses. Our protocol is available on PROSPERO (registration number CRD42023401219). Results A total of 21 were eligible for the systematic review, of which 15 were eligible for meta-analysis. All studies delivered ivermectin through MDA. The pooled prevalence reduction of S. stercoralis following MDA with ivermectin alone was 84.49% (95% CI 54.96–94.66) across five studies and 81.37% (95% CI 61.62–90.96) across seven studies with or without albendazole. The prevalence reduction of T. trichiura was 49.93% (95% CI 18.23–69.34) across five studies with ivermectin alone, and 89.40% (95% CI 73.66–95.73) across three studies with the addition of albendazole. There was high heterogeneity for all syntheses (I 2 > 65%). Conclusions This study underscores the key role of ivermectin-based MDA in addressing limitations in current global STH guidelines in terms of limited efficacy against S. stercoralis and T. trichiura. Based on these findings, revising international STH guidelines to include ivermectin is a promising option to progress the control and eventual elimination of STHs and other NTDs.

Abstract Background Soil-transmitted helminth (STH) infection is driven by a complex interaction of demographic, socioeconomic and behavioural factors, including those related to water, sanitation and hygiene (WASH). Epidemiological studies that measure both infection and potential risk factors associated with infection help to understand the drivers of transmission in a population and therefore can provide information to optimise STH control programmes. Methods During October and November 2019, we conducted a cross-sectional survey of the prevalence and intensity of STH infection and associated risk factors among 7710 primary-school-age children from 64 primary schools across 13 districts in Dak Lak province, Vietnam. Quantitative PCR (qPCR) was used to detect and quantify STH infections. Results The predominant STH species was the hookworm Necator americanus (overall cluster-adjusted prevalence of 13.7%), and its prevalence was heterogeneously distributed across surveyed schools (0% to 56.3%). All other STH species had a prevalence of less than 1%. Using mixed-effects logistic regression, we found that the adjusted odds ratio (aOR) was significantly higher for both infection and moderate-to-heavy-intensity infection with N. americanus among children from multiple ethnic minority groups, compared to children from the majority group (Kinh). Adjusted odds of infection with N. americanus were also higher in children who reported practising open defecation at school (aOR 1.42, 95% CI 1.05, 1.93, P = 0.02) and in those who had an unimproved household water supply (aOR 1.28, 95% CI 1.04, 1.57, P = 0.02). Conversely, children with a flushing household toilet had a reduced risk of infection (aOR 0.58, 95% CI 0.47, 0.70, P

Abstract Dengue fever is a mosquito-borne viral infection, with rising incidence globally. Eastern Ethiopia has had dengue fever outbreaks in recent years. However, the extent to which the infection contributes to hospital presentation among children with fever in southern Ethiopia is unknown. We examined 407 stored plasma samples collected to investigate the aetiology of fever in children aged at least 2 months and under 13 years presenting to the outpatient of the largest tertiary hospital in southern Ethiopia. We analyzed samples for dengue virus non-structural 1 antigen using enzyme-linked immunosorbent assay. The median (interquartile range) age of the 407 children examined was 20 (10–48) months, and 166 (40.8%) of the children were females. Of 407 samples analyzed, 9 (2.2%) were positive for dengue virus non-structural 1 antigen, of whom 2 were initially treated with antimalarial drugs despite having negative malaria microscopy, and 1 of the 8 patients had a persistent fever at the seventh day of follow-up time. The presence of active dengue virus infection in the study area highlights the need for studies at the community level as well as the integration of dengue diagnostics into fever-management strategies. Further research to characterize circulating strains is warranted.

Summary: Background: Soil-transmitted helminth (STH) infection control programs typically consist of school-based preventive chemotherapy (PC) targeted to school-aged children. STH reservoirs in untreated community members contribute to ongoing transmission in children. The CoDe-STH (Community Deworming against STH) trial, conducted in Dak Lak province, Vietnam, between October 2019 and November 2020, aimed to determine whether community-wide mass drug administration (MDA) is more effective than school-based targeted PC in reducing STH prevalence and intensity in children. Methods: In this two-arm cluster randomised controlled trial, 64 primary schools were randomly assigned 1:1 to receive either school-based targeted PC (“school arm”) or community-wide MDA (“community arm”). A single dose of albendazole 400 mg was used for deworming. The primary outcome was hookworm prevalence in schoolchildren, measured using quantitative real-time PCR. We also measured infection intensity for Necator americanus only, using qPCR cycle threshold (Ct) values converted into eggs per gram of faeces (EPG). Analysis was by intention to treat. The trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12619000309189). Findings: The analysis included 4955 children in the school arm and 5093 children in the community arm. N. americanus was the dominant STH species. The relative reduction in hookworm prevalence was not significantly different between the school arm (30.1%, 95% confidence interval [CI] 20.5–36.9) and the community arm (34.6%, 95% CI 19.9–49.4). Due to lower baseline prevalence than expected, the study was underpowered to detect a difference in prevalence reduction between the study arms. The community arm showed significantly greater relative reduction in N. americanus infection intensity (56.0%, 95% CI 39.9–72.1) compared to the school arm (3.4%, 95% CI −24.7 to 31.4). The community arm also showed greater relative reduction in prevalence of moderate-to-heavy intensity (≥2000 EPG) N. americanus infections (81.1%; 95% CI 69.7–92.6) compared to the school arm (39.0%, 95% CI 13.7–64.2). Interpretation: Although no impact was seen on overall prevalence, community-wide MDA was more effective in lowering N. americanus infection intensity in schoolchildren compared to school-based targeted PC, measured 12 months after one round of albendazole deworming with high coverage. Funding: National Health and Medical Research Council, Australia (APP1139561).

Summary: Background: School-based targeted preventive chemotherapy (PC), the main strategy for soil-transmitted helminths (STH) control, excludes other at-risk populations including adults and preschool children. Mass drug administration (MDA), covering all age groups, would bring additional health benefits but also requires greater investment. This cost survey and cost-effectiveness analysis compared MDA with school-based targeted PC for STH control in Dak Lak, Vietnam, where STH are endemic. Methods: A cost survey was conducted in 2020 to estimate the total and per person economic and financial cost of each strategy. Monte Carlo simulation accounted for uncertainty in cost estimates. The primary effectiveness measure was hookworm-related disability-adjusted life years (DALYs) averted, and secondary measures were hookworm infection-years averted and moderate-to-heavy intensity hookworm infection-years averted. A Markov model was used to determine the incremental cost-effectiveness ratio (ICER) of MDA compared to school-based targeted PC using a government payer perspective and a ten-year time horizon. One-way and probabilistic sensitivity analyses (PSA) were performed. Costs are reported in 2020 USD ($). Findings: The economic cost per person was $0.27 for MDA and $0.43 for school-based targeted PC. MDA in Dak Lak will cost $472,000 per year, while school-based targeted PC will cost $117,000. Over 10 years, MDA is estimated to avert an additional 121,465 DALYs; 4,019,262 hookworm infection-years, and 765,844 moderate-to-heavy intensity hookworm infection-years compared to school-based targeted PC. The ICER was $28.55 per DALY averted; $0.87 per hookworm infection-years averted, and $4.54 per moderate-to-heavy intensity hookworm infection-years averted. MDA was cost-effective in all PSA iterations. Interpretation: In areas where hookworm predominates and adults suffer a significant burden of infection, MDA is cost effective compared to school based targeted PC and is the best strategy to achieve global targets. Funding: The project was funded by the National Health and Medical Research Council (NHMRC) of Australia (Project Grant APP1139561) and JPCDT was supported by a UNSW Scientia PhD Scholarship.

BackgroundStrongyloides stercoralis is a neglected soil-transmitted helminth (STH) that leads to significant morbidity in endemic populations. Infection with this helminth has recently been recognised by the World Health Organization (WHO) as a major global health problem to be addressed with ivermectin preventive chemotherapy, and therefore, there is now, the need to develop guidelines for strongyloidiasis control that can be implemented by endemic countries. This study aimed to evaluate the impact of ivermectin preventive chemotherapy (PC) on S. stercoralis prevalence in endemic areas to generate evidence that can inform global health policy.Methodology/principal findingsThis study was a systematic review and meta-analysis. We searched PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and LILACS for literature published between 1990 and 2022 and reporting prevalence of S. stercoralis before and after PC with ivermectin, administered either at school or at community level. The search strategy identified 933 records, eight of which were included in the meta-analysis. Data extraction and quality assessment were carried out by two authors. Meta-analysis of studies based on fecal testing demonstrated a significant reduction of S. stercoralis prevalence after PC: prevalence Risk Ratio (RR) 0.18 (95% CI 0.14-0.23), I2 = 0. A similar trend was observed in studies that used serology for diagnosis: RR 0.35 (95% CI 0.26-0.48), I2 = 4.25%. A sensitivity analysis was carried out for fecal tests where low quality studies were removed, confirming a post-intervention reduction in prevalence. The impact of PC could not be evaluated at different time points or comparing annual vs biannual administration due to insufficient data.Conclusions/significanceOur findings demonstrate a significant decrease of S. stercoralis prevalence in areas where ivermectin PC has taken place, supporting the use of ivermectin PC in endemic areas.

Abstract We assessed the diagnosis, management and outcomes of acute febrile illness in a cohort of febrile children aged under 5 years presenting at one urban and two rural health centres and one tertiary hospital between 11 August 2019 and 01 November 2019. Pneumonia was diagnosed in 104 (30.8%) of 338 children at health centres and 128 (65.0%) of 197 at the hospital (p

BackgroundA school preventive chemotherapy (PC) program for soil-transmitted helminths (STHs) and schistosomiasis has operated in Huambo, Uige and Zaire provinces, Angola, since 2013 and 2014, respectively; complemented by a school water, sanitation and hygiene (WASH) program in a subset of schools from 2016. Conducted in 2021, this is the first impact assessment of the school program for the control of schistosomiasis and STHs.Methodology/principal findingsA two-stage cluster design was used to select schools and schoolchildren for parasitological and WASH surveys. The rapid diagnostic tests (RDTs), point of care circulating cathodic antigen (POC-CCA) and Hemastix, were used to estimate Schistosoma mansoni and Schistosoma haematobium prevalence, respectively. Kato Katz was used to detect STHs, and quantify STH and S. mansoni infections. Urine filtration was used to quantify S. haematobium infections. Prevalence, infection intensity, relative prevalence reduction and egg reduction rates were calculated for schistosomiasis and STHs. Cohen's Kappa co-efficient was used to assess agreement between RDTs and microscopy. Chi-square or Fisher's exact test was used to compare WASH indicators in WASH-supported and WASH-unsupported schools. Overall, 17,880 schoolchildren (599 schools) and 6,461 schoolchildren (214 schools) participated in the schistosomiasis and STH surveys, respectively. Prevalence of any schistosomiasis in Huambo was 29.6%, Uige 35.4%, and Zaire 28.2%. Relative reduction in schistosomiasis prevalence from 2014 for Huambo was 18.8% (95% confidence interval (CI) 8.6, 29.0), Uige -92.3% (95%CI -162.2, -58.3), and Zaire -14.0% (95%CI -48.6, 20.6). Prevalence of any STH in Huambo was 16.3%, Uige 65.1%, and Zaire 28.2%. Relative reduction in STH prevalence for Huambo was -28.4% (95%CI -92.1, 35.2), Uige -10.7% (95%CI -30.2, 8.8), and Zaire -20.9% (95%CI -79.5, 37.8). A higher proportion of WASH-supported schools had improved water sources, and toilet and handwashing facilities compared to WASH-unsupported schools.Conclusions/significanceThe limited impact this school program has had in controlling schistosomiasis and STHs identifies the need for a comprehensive understanding of individual, community, and environmental factors associated with transmission, and consideration for a community-wide control program.

Abstract Background Schistosomiasis and soil-transmitted helminths (STHs) contribute high disease burdens amongst the neglected tropical diseases (NTDs) and are public health problems in Angola. This study reports the prevalence, intensity and risk factors for schistosomiasis and STH infection in Huambo, Uige and Zaire provinces, Angola, to inform a school-based preventive chemotherapy program. Methods A two-stage cluster design was used to select schools and schoolchildren to participate in parasitological and water, sanitation and hygiene (WASH) surveys across Huambo, Uige, and Zaire provinces. Point-of-care circulating cathodic antigen and urinalysis rapid diagnostic tests (RDTs) were used to determine the prevalence of Schistosoma mansoni and S. haematobium, respectively. Kato-Katz was used to identify and quantify STH species and quantify and compare with RDTs for S. mansoni. Urine filtration was used to quantify and compare with RDTs for S. haematobium. Descriptive statistics were used for prevalence and infection intensity of schistosomiasis and STH infection. Performance of RDTs was assessed through specificity and Cohen’s Kappa agreement with microscopy. A multivariate regression analysis was used to determine demographic and WASH factors associated with schistosomiasis and STH infection. Results A total 575 schools and 17,093 schoolchildren participated in the schistosomiasis survey, of which 121 schools and 3649 schoolchildren participated in the STH survey. Overall prevalence of S. mansoni was 21.2% (municipality range 0.9–74.8%) and S. haematobium 13.6% (range 0–31.2%), with an overall prevalence of schistosomiasis of 31.4% (range 5.9–77.3%). Overall prevalence of Ascaris lumbricoides was 25.1% (range 0–89.7%), hookworm 5.2% (range 0–42.6%), and Trichuris trichiura 3.6% (range 0–24.2%), with an overall prevalence of STH infection of 29.5% (range 0.8–89.7%). Ecological zone and ethnicity were factors associated with schistosomiasis and STH infection, with older age and female sex additional risk factors for S. haematobium. Conclusions Most municipalities met World Health Organization defined prevalence thresholds for a schistosomiasis preventive chemotherapy program. A STH preventive chemotherapy program is indicated for nearly all municipalities in Uige and select municipalities in Huambo and Zaire. The association between ecological zone and ethnicity with schistosomiasis and STH infection necessitates further evaluation of home and school environmental, sociodemographic and behavioural factors to inform targeted control strategies to complement preventive chemotherapy programs.

Abstract Background The management of febrile illnesses is challenging in settings where diagnostic laboratory facilities are limited, and there are few published longitudinal data on children presenting with fever in such settings. We have previously conducted the first comprehensive study of infectious aetiologies of febrile children presenting to a tertiary care facility in Ethiopia. We now report on clinicians’ prescribing adherence with guidelines and outcomes of management in this cohort. Methods We consecutively enrolled febrile children aged 2 months and under 13 years, who were then managed by clinicians based on presentation and available laboratory and radiologic findings on day of enrolment. We prospectively collected outcome data on days 7 and 14, and retrospectively evaluated prescribing adherence with national clinical management guidelines. Results Of 433 children enrolled, the most common presenting syndromes were pneumonia and acute diarrhoea, diagnosed in 177 (40.9%) and 82 (18.9%), respectively. Antibacterial agents were prescribed to 360 (84.7%) of 425 children, including 36 (34.0%) of 106 children without an initial indication for antibacterials according to guidelines. Antimalarial drugs were prescribed to 47 (11.1%) of 425 children, including 30 (7.3%) of 411 children with negative malaria microscopy. Fever had resolved in 357 (89.7%) of 398 children assessed at day 7, and in-hospital death within 7 days occurred in 9 (5.9%) of 153 admitted patients. Among children with pneumonia, independent predictors of persisting fever or death by 7 days were young age and underweight for age. Antibacterial prescribing in the absence of a guideline-specified indication (overprescribing) was more likely among infants and those without tachypnea, while overprescribing antimalarials was associated with older age, anaemia, absence of cough, and higher fevers. Conclusion Our study underscores the need for improving diagnostic support to properly guide management decisions and enhance adherence by clinicians to treatment guidelines.

Abstract Background Achieving the elimination of soil-transmitted helminth (STH) infections requires a sufficient understanding of the current epidemiological status of STH endemicity. We aimed to examine the status of STH in Myanmar – a country with the eighth highest STH prevalence in the world, 10 years after instigation of the national deworming programme. Methods In August 2016 we screened for STH infections using Kato Katz (KK) microscopy and real-time PCR (qPCR) in schoolchildren from the Bago Region township of Phyu, a STH sentinel site in Myanmar. Ten schools were randomly selected, and one stool sample each from a total of 264 students was examined. Prevalence and intensity of infection were calculated for each STH. Results High prevalence of STH was identified in the study area with 78.8% of the schoolchildren infected with at least one STH by qPCR, and 33.3% by KK. The most prevalent STH was Trichuris trichiura, diagnosed by both KK (26.1%) and qPCR (67.1%), followed by Ascaris lumbricoides (15.5% KK; 54.9% qPCR). No hookworm infections were identified by KK; however, the qPCR analysis showed a high prevalence of Ancylostoma sp. infection (29.6%) with few Necator americanus (1.1%) infections. Conclusions Despite bi-annual deworming of schoolchildren in the fourth-grade and below, STH prevalence remains stubbornly high. These results informed the expansion of the Myanmar National STH control programme to include all school-aged children by the Ministry of Health and Sports in 2017, however further expansion to the whole community should be considered along with improving sanitation and hygiene measures. This would be augmented by rigorous monitoring and evaluation, including national prevalence surveys.

Abstract Background Scabies causes considerable morbidity in disadvantaged populations. The International Alliance for the Control of Scabies (IACS) published consensus criteria in 2020 to standardize scabies diagnosis. However, these criteria are complex, and a WHO informal consultation proposed simplified criteria for mapping, to identify regions of high prevalence as targets for mass drug administration. We aimed to investigate the accuracy of simplified criteria in determining scabies prevalence, compared to the 2020 IACS criteria. Methods We obtained data relating to demographics, relevant history and skin lesions from all-age prevalence surveys from Fiji (n = 3365) and Solomon Islands (n = 5239), as well as school-aged children in Timor-Leste (n = 1043). We calculated prevalence using the 2020 IACS criteria and simplified criteria and compared these disease estimates. Results There was no significant difference in the pooled prevalence using the two methods (2020 IACS criteria: 16.6%; simplified criteria: 15.6%; difference = 0.9, [95% CI -0.1, 2.0]). In Timor-Leste, the prevalence using simplified criteria was lower (26.5% vs 33.8%). Simplified criteria had a sensitivity of 82.3% (95% CI 80.2, 84.2) and specificity of 97.6% (95% CI 97.2, 97.9) compared to the 2020 IACS criteria. Conclusions The scabies prevalence estimation using simplified criteria was similar to using the 2020 IACS criteria in high prevalence, tropical countries. The prevalence estimation was lower in the school-based survey in Timor-Leste. Mapping using simplified criteria may be a feasible and effective public health tool to identify priority regions for scabies control. Further work assessing use of simplified criteria for mapping in a field setting should be conducted.

Abstract Background Tuberculosis (TB) care can be costly for patients and their families. The End TB Strategy includes a target that zero TB affected households should experience catastrophic costs associated with TB care. Costs are catastrophic when a patient spends 20% or more of their annual household income on their TB diagnosis and care. In Solomon Islands the costs of TB care are unknown. The aim of this study was to determine the costs of TB diagnosis and care, the types of costs and the proportion of patients with catastrophic costs. Methods This was a nationally representative cross-sectional survey of TB patients carried out between 2017 and 2019. Patients were recruited from health care facilities, from all ten provinces in Solomon Islands. During an interview they were asked about the costs of TB diagnosis and care. These data were analysed using descriptive statistics to describe the costs overall and the proportions of different types of costs. The proportion of patients with catastrophic costs was calculated and a multivariate logistic regression was undertaken to determine factors associated with catastrophic costs. Results One hundred and eighty-three TB patients participated in the survey. They spent a mean of 716 USD (inter quartile range: 348–1217 USD) on their TB diagnosis and care. Overall, 62.1% of costs were attributable to non-medical costs, while income loss and medical costs comprised 28.5 and 9.4%, respectively. Overall, 19.7% (n = 36) of patients used savings, borrowed money, or sold assets as a financial coping mechanism. Three patients (1.6%) had health insurance. A total of 92.3% (95% CI: 88.5–96.2) experienced catastrophic costs, using the output approach. Being in the first, second or third poorest wealth quintile was significantly associated with catastrophic costs (adjusted odds ratio: 67.3, 95% CI: 15.86–489.74%, p

Preventive chemotherapy (PC), consisting of the regular distribution of anthelmintics to populations or groups of populations at risk, is the primary tool used to control soil-transmitted helminth (STH) infections. This strategy, whilst cost-effective, raises the concern of potential emergence of drug resistance. The efficacy of anthelmintics against STH infections is measured using cure rate (CR) and egg reduction rate (ERR), using microscopy-based techniques such as the Kato-Katz thick smear. However, Kato-Katz has low sensitivity, especially for low-intensity infections, and requires fresh samples that need to be processed quickly. Realtime quantitative PCR (qPCR), which is more sensitive, is emerging as a "gold standard" for STH diagnostics given its higher sensitivity (important in low prevalence settings) and ability to differentiate hookworm species, while sodium nitrate flotation (SNF) may provide a low-cost more sensitive and practical alternative to Kato-Katz in the field. In this study, we examined the efficacy of a locally manufactured brand of albendazole 400 mg ("Alzental") against hookworm in Đắk Lắk province, Vietnam, using both qPCR and SNF. For qPCR, formulae to convert qPCR cycle threshold (Ct) values into eggs per gram of faeces (EPG) were utilised to determine efficacy calculations, and these values directly compared with efficacy values generated using SNF. Factors associated with CR and ERR were examined, and Alzental tablet quality was assessed by comparing with an Australian TGA-approved equivalent "Eskazole" tablet. We observed a CR and ERR of 64.9% and 87.5% respectively using qPCR, and 68.4% and 67.6% respectively using SNF. The tablet composition of Alzental was comparable to Eskazole in terms of active albendazole drug concentration with no evidence of impurities. This study demonstrates that the efficacy of Alzental against hookworm is within the range of previously reported studies for albendazole 400 mg. The study also demonstrates the value of qPCR and SNF as alternatives to standard Kato-Katz methodology for assessment of anthelmintic efficacy.

BackgroundThe Kato-Katz microscopy technique is the global standard for assessment of soil-transmitted helminth (STH) burden. However, major limitations include its poor sensitivity, requirement for rapid sample processing, and inability to differentiate hookworm species nor detect Strongyloides spp. infections. We assessed the prevalence and intensity of STH species in Solomon Islands by conducting a province-wide survey using quantitative PCR (qPCR) for diagnosis, which can provide much better characterisation of STH burden than microscopy.Methodology/principal findingsWe conducted a cross-sectional survey in 18 villages in Western Province to detect infections with six STH species and quantify intensity with three. We used linear mixed model regression to identify potential water, sanitation, and hygiene (WASH) and environmental risk factors for infection. We collected stool specimens from 830 village residents. Overall STH prevalence was 63.3% (range 27.5 to 91.5% across villages), led by Necator americanus (54.5% [range 17.5-89.4%]), followed by Ancylostoma ceylanicum (15.5% [range 2.8-45.8%]), Trichuris trichiura (9.1% [range 0-79.2%]), and Strongyloides spp. (3.2% [range 0-29.2%]). Most infections were of light intensity for N. americanus (85.7%) and T. trichiura (90.7%). Owning a household latrine was associated with a lower risk of N. americanus infection (AOR 0.41, 95% CI 0.24-0.68) while greater precipitation was linked to more common T. trichiura infection (AOR 1.14, 95% CI 1.04-1.25).Conclusion/significanceIn this first large-scale population survey of STH in the Pacific using qPCR, we found evidence that ivermectin should be incorporated into STH control programmes because of the presence of T. trichiura and Strongyloides spp., both of which are poorly responsive to albendazole. Furthermore, One Health strategies are needed for improved A. ceylanicum and Strongyloides spp. control, WASH access and use should be improved to complement deworming programmes, and control efforts should ideally be expanded to entire communities.Trial registrationClinicalTrials.gov Australian and New Zealand Clinical Trials Registry ACTRN12618001086257.

Background The epidemiology of trachoma in several Pacific Islands differs from other endemic settings, in that there is a high prevalence of clinical signs of trachoma, particularly trachomatous inflammation—follicular (TF), but few cases of trichiasis and limited evidence of ocular chlamydial infection. This so-called “Pacific enigma” has led to uncertainty regarding the appropriate public health response. In 2019 alongside Nauru’s national trachoma population survey, we performed bacteriological and serological assessments of children to better understand the typology of trachoma and to determine whether there is a need for trachoma interventions. Methods We used two-stage cluster sampling, examining residents aged ≥1 year and collecting household-level water, sanitation, and hygiene (WASH) variables. Children aged 1–9 years provided conjunctival swabs and finger-prick dried blood spots to investigate the presence of Chlamydia trachomatis nucleic acid and anti-Pgp3 antibodies, respectively. Principal Findings In 818 participants aged 1–9 years, the age-adjusted TF prevalence was 21.8% (95% CI 15.2–26.2%); ocular C. trachomatis prevalence was 34.5% (95% CI 30.6–38.9), and anti-Pgp3 antibody prevalence was 32.1% (95% CI 28.4%–36.3%). The age- and gender-adjusted prevalence of trichiasis in ≥15-year-olds was 0.3% (95% CI 0.00–0.85), but no individual with trichiasis had trachomatous scarring (TS). Multivariable analysis showed an association between age and both TF (OR per year of age 1.3 [95% CI 1.2–1.4]) and anti-Pgp3 positivity (OR 1.2 [95% CI 1.2–1.3]). There were high rates of access to water and sanitation and no WASH variable was associated with the presence of TF. Conclusions TF, nucleic acid, and age-specific antibody prevalence collectively indicate that high levels of C. trachomatis transmission among children present a high risk of ocular damage due to trachoma. The absence of trichiasis with trachomatous scarring suggest a relatively recent increase in transmission intensity. Author summary In contrast to several neighbouring Pacific Island nations, Nauruan children are heavily affected by active trachoma and the cause is ocular infection with C. trachomatis. Comprehensive public health intervention to control trachoma in Nauru is required. The use of laboratory markers for current and previous C. trachomatis infection should be considered in baseline trachoma prevalence surveys as we approach global elimination of trachoma, and in settings with inconsistent findings during previous screening exercises.

Abstract Background Scabies and impetigo are endemic in many tropical, low- and middle-income countries. Mass drug administration (MDA) with ivermectin has emerged as a control strategy for these conditions. In 2019, Timor-Leste Ministry of Health planned to implement MDA including ivermectin for the control of lymphatic filariasis, so we undertook a baseline assessment of scabies and impetigo to better understand local epidemiology and contribute to future surveys assessing the impact of MDA. Methods A cross-sectional school survey was conducted in April–May 2019 at six primary schools in a semi-urban (Dili) and two rural (Ermera and Manufahi) settings. Children under 19 years of age present at school on survey days were eligible to participate, of whom we enrolled 1183. Trained health workers interviewed and examined 1043 participants to clinically diagnose scabies using the 2020 International Alliance for the Control of Scabies (IACS) diagnostic criteria, as well as impetigo. Prevalence was adjusted for age and sex. Mixed-effects logistic regression models were used to analyse odds of scabies and impetigo infection. All models accounted for clustering at the school level through the use of random effect terms. Population attributable risk of scabies as a cause of impetigo was also estimated. Results The overall weighted prevalence of scabies was 30.6%. Children in rural Manufahi were more likely to have scabies than those in semi-urban Dili (53.6% vs 28.2%, adjusted odds ratio [AOR] 3.5). Most cases of scabies were mild (3 to 10 lesions), and lesions were usually distributed on more than one body region. Scabies prevalence was lower among 10 to 14 year olds compared to 5 to 9 year olds. Overall weighted prevalence of impetigo was 11.3%. Relative to Dili, children in rural Ermera and Manufahi were twice as likely to have impetigo. Impetigo was twice as common in children with scabies than in those without, corresponding to an attributable risk of scabies as a cause of impetigo of 22.7%. Conclusions Scabies and impetigo prevalence in Timor-Leste is among the highest reported globally, particularly in rural areas. Scabies infestation was strongly associated with impetigo. Comprehensive control strategies are urgently needed in Timor-Leste.

Abstract Background The diagnosis of non-malarial aetiologies, which now represent the majority of febrile illnesses, has remained problematic in settings with limited laboratory capacity. We aimed to describe common aetiologies of acute febrile illness among children in a setting where malaria transmission has declined. Methods A prospective cross-sectional study was conducted among children aged at least 2 months and under 13 years presenting with fever (temperature of ≥37.5 °C or a history of fever in the past 48 h) to Hawassa Comprehensive Specialized Hospital, southern Ethiopia, from May 2018 through February 2019. Clinical and demographic data were gathered for consecutive participants, and malaria microscopy, HIV testing, and blood and urine cultures were performed regardless of clinical presentation. Additionally, stool analyses (culture and rotavirus/adenovirus RDT) and throat swab for group A Streptococcus (GAS) and urine Streptococcus pneumoniae were performed by RDTs for children with specific conditions. The antimicrobial susceptibility of bacterial isolates was determined using disc diffusion method. Results During the study period 433 children were recruited, median age 20 months (range, 2 months – 12 years) and 178 (41.1%) female. Malaria was diagnosed in 14 (3.2%) of 431 children, and 3 (0.7%) had HIV infection. Bacteraemia or fungaemia was detected in 27 (6.4%) of 421 blood cultures, with Staphylococcus aureus isolated in 16 (3.8%). Urinary tract infections (UTIs) were detected in 74 (18.4%) of 402, with Escherichia coli isolated in 37 (9.2%). Among 56 children whose stool specimens were tested, 14 (25%) were positive for rotavirus, 1 (1.8%) for Salmonella Paratyphi A, and 1 (1.8%) for Shigella dysenteriae. Among those with respiratory symptoms, a throat swab test for GAS and urine test for S. pneumoniae were positive in 28 (15.8%) of 177 and 31 (17.0%) of 182, respectively. No test was positive for a pathogen in 266 (61.4%) of 433 participants. Bacterial isolates were frequently resistant to ampicillin, trimethoprim-sulfamethoxazole, tetracycline, and amoxicillin and clavulanic acid. Conclusion Our results showed low proportions of malaria and bacteraemia among febrile children. In contrast, the frequent detection of UTI emphasize the need to support enhanced diagnostic capacity to ensure appropriate antimicrobial intervention.

Background Preventative chemotherapy and mass drug administration have been identified as effective strategies for the prevention, treatment, control and elimination of several NTDs in the Asia-Pacific region. Qualitative research can provide in-depth insight into the social dynamics and processes underlying effective implementation of and adherence to mass drug administration programs. This scoping review examines published qualitative literature to examine factors influencing community perceptions and acceptability of mass drug administration approaches to control NTDs in the Asia-Pacific region. Methodology Twenty-four peer reviewed published papers reporting qualitative data from community members and stakeholders engaged in the implementation of mass drug administration programs were identified as eligible for inclusion. Findings This systematic scoping review presents available data from studies focussing on lymphatic filariasis, soil-transmitted helminths and scabies in eight national settings (India, Indonesia, Philippines, Bangladesh, Laos, American Samoa, Papua New Guinea, Fiji). The review highlights the profoundly social nature of individual, interpersonal and institutional influences on community perceptions of willingness to participate in mass drug administration programs for control of neglected tropical diseases (NTD). Future NTD research and control efforts would benefit from a stronger qualitative social science lens to mass drug administration implementation, a commitment to understanding and addressing the social and structural determinants of NTDs and NTD control in complex settings, and efforts to engage local communities as equal partners and experts in the co-design of mass drug administration and other efforts to prevent, treat, control and eliminate NTDs. Conclusion For many countries in the Asia-Pacific region, the “low hanging fruit has been picked” in terms of where mass drug administration has worked and transmission has been stopped. The settings that remain–such as remote areas of Fiji and Papua New Guinea, or large, highly populated, multi-cultural urban settings in India and Indonesia–present huge challenges going forward. Author summary Qualitative research can provide in-depth insight into the social dynamics and processes underlying effective implementation of and adherence to mass drug administration programs. This scoping review examines published qualitative literature to examine factors influencing community perceptions and acceptability of mass drug administration approaches to control neglected tropical diseases (NTDs) in the Asia-Pacific region. Our analyses highlight the profoundly social nature of individual, interpersonal and institutional influences on community perceptions of willingness to participate in mass drug administration programs for control of NTDs. For many countries in the Asia-Pacific region, the “low hanging fruit has been picked” in terms of where mass drug administration has worked and transmission has been stopped. The settings that remain–e.g. remote areas of Fiji and Papua New Guinea, or large, highly populated, multi-cultural urban settings in India and Indonesia–present huge challenges going forward. Future NTD research and control efforts would benefit from a stronger qualitative social science lens to mass drug administration implementation, a commitment to understanding the socio-structural determinants of NTDs and NTD control in complex settings, and engaging local communities as equal partners and experts in the co-design of mass drug administration and other efforts to prevent, treat, control and eliminate NTDs.

BackgroundTimely health care seeking with access to quality health care are crucial to improve child survival. We conducted a study which aimed to identify factors influencing timely health care seeking and choice of first source of health care in Ethiopia.MethodsA total of 535 caregivers who sought health care for febrile children aged under 5 years at a tertiary hospital, and one urban and two rural health centres in Hawassa, southern Ethiopia were recruited to participate in the study from August to November 2019. Caregivers were interviewed using pretested structured questionnaires on socio-demographic and clinical factors to identify associations with health care seeking practice and first source of care, and reasons for particular practices. Delayed care seeking was defined as seeking care from a health facility after 24 hours of onset of fever.ResultsOf 535 caregivers who participated, 271 (50.7%) had sought timely health care; 400 (74.8%) utilized a primary health care (PHC) facility as first source; and 282 (52.7%) bypassed the nearest PHC facility. Rural residents (adjusted odds ratio (AOR) 1.85; 95% CI 1.11-3.09), and those who reported cough (AOR 1.87; 95% CI 1.20-2.93) as a reason for consultation were more likely to delay seeking health care. While caregivers were less likely delayed for children aged 24-35 months (AOR 0.50; 95% CI 0.28-0.87) compared to infants. Utilizing higher-level hospitals as the first source of care was less frequent among rural residents (AOR 0.15; 95% CI 0.06-0.39) and in those with no formal education (AOR 0.03; 95% CI 0.01-0.27). Those having a longer travel time to the provider (AOR 2.11; 95% CI 1.09-4.08) more likely utilized higher hospitals.ConclusionWe identified a need to improve timely health seeking among rural residents, infants, and those presenting with respiratory symptoms. Improvements may be achieved by educating communities on the need of early care seeking, and ensuring the communities members' expectations of services at each level consistent with the services capacity.

Abstract Background Giardiasis is a common diarrhoeal disease caused by the protozoan Giardia duodenalis. It is prevalent in low-income countries in the context of inadequate access to water, sanitation and hygiene (WASH), and is frequently co-endemic with neglected tropical diseases such as soil-transmitted helminth (STH) infections. Large-scale periodic deworming programmes are often implemented in these settings; however, there is limited evidence for the impact of regular anthelminthic treatment on G. duodenalis infection. Additionally, few studies have examined the impact of WASH interventions on G. duodenalis. Methods The WASH for WORMS cluster randomised controlled trial was conducted in remote communities in Manufahi municipality, Timor-Leste, between 2012 and 2016. All study communities received four rounds of deworming with albendazole at six-monthly intervals. Half were randomised to additionally receive a community-level WASH intervention following study baseline. We measured G. duodenalis infection in study participants every six months for two years, immediately prior to deworming, as a pre-specified secondary outcome of the trial. WASH access and behaviours were measured using questionnaires. Results There was no significant change in G. duodenalis prevalence in either study arm between baseline and the final study follow-up. We found no additional benefit of the community-level WASH intervention on G. duodenalis infection (relative risk: 1.05, 95% CI: 0.72–1.54). Risk factors for G. duodenalis infection included living in a household with a child under five years of age (adjusted odds ratio, aOR: 1.35, 95% CI: 1.04–1.75), living in a household with more than six people (aOR: 1.32, 95% CI: 1.02–1.72), and sampling during the rainy season (aOR: 1.23, 95% CI: 1.04–1.45). Individuals infected with the hookworm Necator americanus were less likely to have G. duodenalis infection (aOR: 0.71, 95% CI: 0.57–0.88). Conclusions Prevalence of G. duodenalis was not affected by a community WASH intervention or by two years of regular deworming with albendazole. Direct household contacts appear to play a dominant role in driving transmission. We found evidence of antagonistic effects between G. duodenalis and hookworm infection, which warrants further investigation in the context of global deworming efforts. Trial registration Australian New Zealand Clinical Trials Registry, ACTRN12614000680662. Registered 27 June 2014, retrospectively registered. https://anzctr.org.au/Trial/Registration/TrialReview.aspx?id=366540.

ObjectiveTo estimate the impact of preventive chemotherapy on the prevalence and intensity of soil-transmitted helminth (STH) infections, schistosomiasis, and lymphatic filariasis in the Philippines, using systematic review and meta-analysis.MethodsWe included reports reporting prevalence of STH infections, schistosomiasis, or lymphatic filariasis in the Philippines published until 31 March 2021. Peer-reviewed studies were identified in electronic databases. Grey literature reports by the University of the Philippines and the Department of Health were also included. Pooled infection prevalence, before and after the initiation of preventive chemotherapy, stratified by age group, was calculated using the inverse variance heterogeneity model.FindingsA total of 109 reports were included in the review and meta-analysis. Overall prevalence of moderate-heavy intensity Ascaris lumbricoides (6.6%) and Trichuris trichiura (2.7%) infection after initiation of preventive chemotherapy were significantly lower than the prevalence prior to initiation (23.6% for A. lumbricoides and 12.2% for T. trichiura). Prevalence reductions were also found in school and preschool-age children for A. lumbricoides and T. trichiura. Studies conducted after preventive chemotherapy initiation had significantly lower overall prevalence of moderate-heavy intensity schistosomiasis (3.1% vs 0.2%) and of schistosomiasis in school-age children (30.5% vs 1%). Pooled prevalence of lymphatic filariasis prior to preventive chemotherapy initiation was 3.2% across 12 provinces, while currently only two provinces still have prevalence of more than 1%. There were no published studies reporting prevalence of lymphatic filariasis after initiation of preventive chemotherapy. Heterogeneity was high with I2 mostly above 90%.ConclusionThe burden of STH infections and schistosomiasis in children were significantly lower in studies conducted following the initiation of preventive chemotherapy. Eliminating morbidity and interrupting transmission, however, may require expanded control initiatives including community-wide treatment, and improved water, sanitation, and hygiene. Lymphatic filariasis burden has decreased since the implementation of preventive chemotherapy, with all but two provinces having reached the elimination of lymphatic filariasis as a public health problem.

Introduction Tungiasis (sand flea disease or jigger infestation) is a neglected tropical disease caused by penetration of female sand fleas, Tunga penetrans, in the skin. The disease inflicts immense pain and suffering on millions of people, particularly children, in Latin America, the Caribbean and sub-Saharan Africa. Currently, there is no standard treatment for tungiasis, and a simple, safe and effective tungiasis treatment option is required. Tea tree oil (TTO) has long been used as a parasiticidal agent against ectoparasites such as headlice, mites and fleas with proven safety and efficacy data. However, current data are insufficient to warrant a recommendation for its use in tungiasis. This trial aims to generate these data by comparing the safety and efficacy of a 5% (v/w) TTO proprietary gel formulation with 0.05% (w/v) potassium permanganate (KMnO4) solution for tungiasis treatment.Methods and analysis This trial is a randomised controlled trial (RCT) in primary schools (n=8) in South-Western Kenya. The study will include school children (n=88) aged 6–15 years with a confirmed diagnosis of tungiasis. The participants will be randomised in a 1:1 ratio to receive a 3-day two times a day treatment of either 5% TTO gel or 0.05% KMnO4 solution. Two viable embedded sandflea lesions per participant will be targeted and the viability of these lesions will be followed throughout the study using a digital handheld microscope. The primary outcome is the proportion of observed viable embedded sand fleas that have lost viability (non-viable lesions) by day 10 (9 days after first treatment). Secondary outcomes include improvement in acute tungiasis morbidities assessed using a validated severity score for tungiasis, safety assessed through adverse events and product acceptability assessed by interviewing the participants to rate the treatment in terms of effectiveness, side effects, convenience, suitability and overall satisfaction.Ethics and dissemination The trial protocol has been reviewed and approved by the University of Canberra Human Research Ethics Committee (HREC-2019-2114). The findings of the study will be presented at scientific conferences and published in a peer-reviewed journal.Trial registration numbers Australian New Zealand Clinical Trials Registry (ACTRN12619001610123); PACTR202003651095100 and U1111-1243-2294.

Invasive bacterial infections are a leading cause of death in children, primarily in low- and middle-income countries (LMIC). Links between carriage of antimicrobial-resistant organisms and more resistant infections have been established; however, little has been reported regarding community carriage of antibiotic-resistant organisms such as extended-spectrum β-lactamase (ESBL)-producing Enterobacterales in LMIC. The aim of this study was to determine colonic carriage of ESBL-producing fluoroquinolone- and aminoglycoside-resistant Enterobacterales in healthy children in three municipalities of Timor-Leste. In November 2020, 621 stool samples were collected from school-aged children and underwent screening for the presence of Enterobacterales species and antimicrobial resistance (AMR). Ciprofloxacin-resistant Gram-negative organisms were cultured from 16.5% (95% CI 6.2–26.9), and gentamicin resistance was identified in 6.8% (95% CI 2.8–10.7). Compared to the prevalence of ciprofloxacin resistance in Dili (36.1%), there was significantly lower prevalence in the rural municipalities of Ermera (12.9%; AOR 0.38, 95% CI 0.24–0.60, p < 0.001) and Manufahi (4.5%; AOR 0.07, 95% CI 0.01–0.51, p = 0.009). The overall cluster-adjusted prevalence of ESBL-producing bacteria was 8.3%, with no significant differences between municipalities. This study demonstrates high rates of carriage of AMR among school-aged children in Timor-Leste, with higher rates observed in Dili compared to rural municipalities. Empiric antibiotic guidelines should include recommendations for treating community-acquired infections that account for the possibility of antimicrobial resistance.

Abstract Background Current guidelines and targets for soil-transmitted helminth (STH) control focus on school-based deworming for school-age children, given the high risk of associated morbidity in this age group. However, expanding deworming to all age groups may achieve improved STH control among both the community in general and school-age children, by reducing their risk of reinfection. This trial aims to compare school-based targeted deworming with community-wide mass deworming in terms of impact on STH infections among school-age children. Methods The CoDe-STH (Community Deworming against STH) trial is a cluster-randomised controlled trial (RCT) in 64 primary schools in Dak Lak province, Vietnam. The control arm will receive one round of school-based targeted deworming with albendazole, while in the intervention arm, community-wide mass deworming with albendazole will be implemented alongside school-based deworming. Prevalence of STH infections will be measured in school-age children at baseline and 12 months following deworming. The primary outcome is hookworm prevalence in school-age children at 12 months, by quantitative PCR. Analysis will be intention-to-treat, with outcomes compared between study arms using generalised linear and non-linear mixed models. Additionally, cost-effectiveness of mass and targeted deworming will be calculated and compared, and focus group discussions and interviews will be used to assess acceptability and feasibility of deworming approaches. Individual based stochastic models will be used to predict the impact of mass and targeted deworming strategies beyond the RCT timeframe to assess the likelihood of parasite population ‘bounce-back’ if deworming is ceased due to low STH prevalence. Discussion The first large-scale trial comparing mass and targeted deworming for STH control in South East Asia will provide key information for policy makers regarding the optimal design of STH control programs. Trial registration ACTRN12619000309189.

Abstract Background Acute undifferentiated febrile illness (AUFI) is caused by a multitude of diverse pathogens, with significant morbidity and mortality in the developing world. The objective of this review was to characterise the diversity and relative importance of common infectious aetiologies of AUFI in South and Southeast Asia. Methods We conducted a comprehensive literature review to identify common aetiologies of AUFI in Asian countries. Four medical and life sciences databases including PubMed, Medline, Embase and Cochrane Central, and Google Scholar were searched for articles published from January 1998 to March 2019. Results Forty-three studies met the inclusion criteria. Among AUFI cases, viral aetiologies at 18.5% (14888) were more common than bacterial aetiologies (12.9% [10384]). From 80,554 cases, dengue fever was the most common aetiology (11.8%, 9511), followed by leptospirosis (4.4%, 3549), typhoid (4.0%, 3258), scrub typhus (4.0%, 3243) and influenza other than H1N1 (3.1%, 2514). In both adults and children: dengue fever was the leading cause of AUFI with 16.6% (1928) and 18.7% (1281) of the total cases. In admitted patients, dengue fever was the main cause of AUFI at 16.4% (2377), however leptospirosis at 13.9% (2090) was the main cause of AUFI for outpatients. In South Asia, dengue fever was the main cause of AUFI, causing 12.0% (6821) of cases, whereas in Southeast Asia, leptospirosis was the main diagnosis, causing 12.1% (2861) of cases. Conclusions In this study the most common causes of AUFI were viral, followed by bacterial and protozoal (malaria) infections. Dengue was the commonest virus that caused AUFI while leptospirosis and typhoid were important bacterial infectious causes. Therefore, it is imperative to maintain a sound epidemiological knowledge of AUFI so that evidence-based diagnostic criteria and treatment guidelines can be developed.

Abstract The transmission soil transmitted helminths (STH) occurs via ingestion of or contact with infective stages present in soil contaminated with human faeces. It follows therefore that efforts to reduce faecal contamination of the environment should help to reduce risk of parasite exposure and improvements in water, sanitation and hygiene (WASH) are seen as essential for the long-term, sustainable control of STH. However, the link between WASH and STH is not always supported by the available evidence from randomised controlled trials, which report mixed effects of WASH intervention on infection risk. This review critically summarises the available trial evidence and offers an interpretation of the observed heterogeneity in findings. The review also discusses the implications of findings for control programmes and highlights three main issues which merit further consideration: intervention design, exposure assessment, and intervention fidelity assessment.

Preventive chemotherapy campaigns with praziquantel and albendazole are being implemented in Angola, as a high priority public health intervention. However, there are no published data regarding adverse events associated with these medications. In this context, we analysed adverse events due to co-administration of praziquantel and albendazole in endemic areas of schistosomiasis and soil-transmitted helminths in Bengo, Angola. In the context of a targeted drug administration, between December 2012 and September 2013, we conducted two surveys after co-administrating single oral doses of praziquantel and albendazole tablets to children 2 to 15 years of age. About 24 hours after each treatment, participants answered a questionnaire about adverse events. At baseline, 605 children (55.0% male; mean age: 9.7 years) were treated; 460 were interviewed and 257 (55.9%) reported at least one adverse event, 62.3% (160/257) of children being infected with schistosoma haematobium. After six months of treatment, among 339 children surveyed, 184 (54.3%) reported adverse events, with 49.5% (91/184) of infected children. Adverse events were most common in preschool-aged children, with no significant difference between genders. The most frequent adverse events in the two surveys were abdominal pain (18.5%, 25.7%), headache (20.9%, 23.0%) and dizziness (15.7%, 19.8%). Children aged 12 to 15 years (adjusted OR = 0.40, p = 0.040) and those with mixed infection (adjusted OR = 0.04, p = 0.011) had lower odds of adverse events. After the second treatment, those with heavy infection (adjusted OR = 2.72, p = 0.018) and aged 9-11 years (adjusted OR = 2.01, p = 0.049) had significantly fewer adverse events. About 2.0% of children experienced severe adverse events. This study adds evidence that preventive chemotherapy for schistosomiasis and soil-transmitted helminths control is safe, but cases of adverse events are expected. Standardized methodologies to discriminate drug-related adverse events from the clinical manifestations of the infections are needed.

BackgroundSchistosomiasis is a widespread public health concern in the poorest regions of the world. The principal control strategy is regular praziquantel administration to school-aged children in endemic areas. With calls for the elimination of schistosomiasis as a public health problem, expanding praziquantel delivery to all community members has been advocated. This systematic review and meta-analysis compares the impact of community-wide and child-targeted praziquantel distribution on schistosomiasis prevalence and intensity in school-aged children.Methodology/principal findingsWe searched MEDLINE, Embase and Web of Science to identify papers that reported schistosome prevalence before and after praziquantel administration, either to children only or to all community members. Extracted data included Schistosoma species, drug administration strategy, number of treatment rounds, follow-up interval and prevalence and intensity before and after treatment. We used inverse variance weighted generalised linear models to examine the impact of mass versus targeted drug administration on prevalence reduction, and weighted boxplots to examine the impact on infection intensity reduction. This study is registered with PROSPERO, number CRD42018095377. In total, 34 articles were eligible for systematic review and 28 for meta-analysis. Schistosoma mansoni was reported in 20 studies; Schistosoma haematobium in 19 studies, and Schistosoma japonicum in two studies. Results of generalised linear models showed no detectable difference between mass and targeted treatment strategies on prevalence reduction in school-aged children for S. mansoni (odds ratio 0.47, 95%CI 0.13-1.68, p = 0.227) and S. haematobium (0.41, 95%CI 0.06-3.03, p = 0.358). Box plots also showed no apparent differences in intensity reduction between the two treatment strategies.Conclusions/significanceThe results of this meta-analysis do not support the hypothesis that community-wide treatment is more effective than targeted treatment at reducing schistosomiasis infections in children. This may be due to the relatively small number of included studies, insufficient treatment coverage, persistent infection hotspots and unmeasured confounders. Further field-based studies comparing mass and targeted treatment are required.

Abstract Background Soil-transmitted helminths (STHs) including Ascaris lumbricoides, Necator americanus, Ancylostoma spp. and Trichuris trichiura are cause of significant global morbidity. To mitigate their disease burden, at-risk groups in endemic regions receive periodic mass drug administration using anthelmintics, most commonly albendazole and mebendazole. Assessing the efficacy of anthelmintic drugs is important for confirming that these regimens are working effectively and that drug resistance has not emerged. In this study we aimed to characterise the therapeutic efficacy of albendazole against Ascaris spp. and N. americanus in Timor-Leste, using a quantitative polymerase chain reaction (qPCR) method for parasite detection and quantification. Results A total of 314 participants from 8 communities in Timor-Leste provided stool samples before and 10–14 days after the administration of a single 400 mg dose of albendazole. Helminth infection status and infection intensity (measured in Ct-values and relative fluorescence units) were determined using qPCR. Efficacy was determined by examining the cure rates and infection intensity reduction rates. Albendazole was found to be highly efficacious against Ascaris spp., with a cure rate of 91.4% (95% CI: 85.9–95.2%) and infection intensity reduction rate of 95.6% (95% CI: 88.3–100%). The drug was less efficacious against N. americanus with a cure rate of 58.3% (95% CI: 51.4–64.9%) and infection intensity reduction rate of 88.9% (95% CI: 84.0–97.0%). Conclusions The observed cure rates and infection intensity reduction rates obtained for Ascaris spp. and to a lower extent N. americanus, demonstrate the continued efficacy of albendazole against these species and its utility as a mass chemotherapy agent in Timor-Leste. Furthermore, this study demonstrates the usefulness of qPCR as a method to measure the efficacy of anthelminthic drugs. Additional research is necessary to translate Ct-values into eggs per gram in a systematic way. Trial registration Australian and New Zealand Clinical Trials Registry 12614000680662 (registered 27 June 2014).

Abstract Background Dengue remains an important public health problem in Timor-Leste, with several major epidemics occurring over the last 10 years. The aim of this study was to identify dengue clusters at high geographical resolution and to determine the association between local environmental characteristics and the distribution and transmission of the disease. Methods Notifications of dengue cases that occurred from January 2005 to December 2013 were obtained from the Ministry of Health, Timor-Leste. The population of each suco (the third-level administrative subdivision) was obtained from the Population and Housing Census 2010. Spatial autocorrelation in dengue incidence was explored using Moran’s I statistic, Local Indicators of Spatial Association (LISA), and the Getis-Ord statistics. A multivariate, Zero-Inflated, Poisson (ZIP) regression model was developed with a conditional autoregressive (CAR) prior structure, and with posterior parameters estimated using Bayesian Markov chain Monte Carlo (MCMC) simulation with Gibbs sampling. Results The analysis used data from 3206 cases. Dengue incidence was highly seasonal with a large peak in January. Patients ≥ 14 years were found to be 74% [95% credible interval (CrI): 72–76%] less likely to be infected than those

Soil-transmitted helminths (STH) are a major cause of morbidity in tropical developing countries with a global infection prevalence of more than one billion people and disease burden of around 3.4 million disability adjusted life years. Infection prevalence directly correlates to inadequate sanitation, impoverished conditions and limited access to public health systems. Underestimation of infection prevalence using traditional microscopy-based diagnostic techniques is common, specifically in populations with access to benzimidazole mass treatment programs and a predominance of low intensity infections. In this study, we developed a multiplexed-tandem qPCR (MT-PCR) tool to identify and quantify STH eggs in stool samples. We have assessed this assay by measuring infection prevalence and intensity in field samples of two cohorts of participants from Timor-Leste and Cambodia, which were collected as part of earlier epidemiological studies. MT-PCR diagnostic parameters were compared to a previously published multiplexed qPCR for STH detection. The MT-PCR assay agreed strongly with qPCR data and showed a diagnostic specificity of 99.60-100.00% (sensitivity of 83.33-100.00%) compared to qPCR and kappa agreement exceeding 0.85 in all tests. In addition, the MT-PCR has the added advantage of distinguishing Ancylostoma spp. species, namely Ancylostoma duodenale and Ancylostoma ceylanicum. This semi-automated platform uses a standardized, manufactured reagent kit, shows excellent run-to-run consistency/repeatability and supports high-throughput detection and quantitation at a moderate cost.

BackgroundRegular preventive chemotherapy (PCT) targeting high-risk populations is an effective way to control STH in the short term, but sustainable long-term STH control is expected to require improved access to water, sanitation, and hygiene (WASH). However, experimental studies have not been able to conclusively demonstrate the benefit of WASH in preventing STH (re-)infections. We investigated the impact of WASH on STH infections during and after PCT using mathematical modelling.Methods and findingsWe use the individual-based transmission model WORMSIM to predict the short and long-term impact of WASH on STH transmission in contexts with and without PCT. We distinguish two WASH modalities: sanitation, which reduces individuals' contributions to environmental contamination; and hygiene, which reduces individuals' exposure to infection. We simulate the impact of varying levels of uptake and effectiveness of each WASH modality, as well as their combined impact. Clearly, sanitation and hygiene interventions have little observable short-term impact on STH infections levels in the context of PCT. However, in the long term, both are pivotal to sustain control or eliminate infection levels after scaling down or stopping PCT. The impact of hygiene is determined more by the effectiveness of the intervention than its overall uptake, whereas the impact of sanitation depends more directly on the product of uptake and the effectiveness.InterpretationThe impact of WASH interventions on STH transmission highly depends on the worm species, WASH modality, and uptake and effectiveness of the intervention. Also, the impact of WASH is difficult to measure in the context of ongoing PCT programmes. Still, we show a clear added benefit of WASH to sustain the gains made by PCT in the long term, such that PCT may be scaled down or even stopped altogether. To safely stop or scale down PCT, policy for WASH and PCT should be integrated.

Abstract Background The Dande Health and Demographic Surveillance System (HDSS) located in Bengo Province, Angola, covers nearly 65,500 residents living in approximately 19,800 households. This study aims to describe the main causes of deaths (CoD) occurred within the HDSS, from 2009 to 2012, and to explore associations between demographic or socioeconomic factors and broad mortality groups (Group I—Communicable diseases, maternal, perinatal and nutritional conditions; Group II—Non-communicable diseases; Group III—Injuries; IND—Indeterminate). Methods Verbal Autopsies (VA) were performed after death identification during routine HDSS visits. Associations between broad groups of CoD and sex, age, education, socioeconomic position, place of residence and place of death, were explored using chi-square tests and fitting logistic regression models. Results From a total of 1488 deaths registered, 1009 verbal autopsies were performed and 798 of these were assigned a CoD based on the 10th revision of the International Classification of Diseases (ICD-10). Mortality was led by CD (61.0 %), followed by IND (18.3 %), NCD (11.6 %) and INJ (9.1 %). Intestinal infectious diseases, malnutrition and acute respiratory infections were the main contributors to under-five mortality (44.2 %). Malaria was the most common CoD among children under 15 years old (38.6 %). Tuberculosis, traffic accidents and malaria led the CoD among adults aged 15–49 (13.5 %, 10.5 % and 8.0 % respectively). Among adults aged 50 or more, diseases of the circulatory system (23.2 %) were the major CoD, followed by tuberculosis (8.2 %) and malaria (7.7 %). CD were more frequent CoD among less educated people (adjusted odds ratio, 95 % confidence interval for none vs. 5 or more years of school: 1.68, 1.04–2.72). Conclusion Infectious diseases were the leading CoD in this region. Verbal autopsies proved useful to identify the main CoD, being an important tool in settings where vital statistics are scarce and death registration systems have limitations.

Rotavirus group A (RVA) is considered the leading cause of pediatric diarrhea, responsible for the high burden of diarrheal diseases in sub-Saharan Africa. Despite recent studies, the existent data are scarce for some African countries like Angola, a country with one of the highest RVA-related death estimates. The aim of this study was to determine the RVA detection rate and circulating genotypes in children less than five years of age with acute gastroenteritis attended at the Bengo General Hospital in Caxito, Bengo province, Angola, before vaccine introduction.Between September 2012 and December 2013, 342 fecal specimens were collected from children enrolled. Positive samples for RVA by immunochromatographic rapid test were G and P-typed by hemi-nested type-specific multiplex PCR, and subgrouped for the VP6 gene. VP4 and VP7 genes from a subset of samples were sequenced for phylogenetic analysis.During the study period, a high RVA detection rate was registered (25.1%, 86/342). The age group most affected by RVA infection includes children under 6 months of age (p

Anaemia is known to have an impact on child development and mortality and is a severe public health problem in most countries in sub-Saharan Africa. We investigated the consistency between ecological and individual-level approaches to anaemia mapping by building spatial anaemia models for children aged ≤15 years using different modelling approaches. We aimed to (i) quantify the role of malnutrition, malaria, Schistosoma haematobium and soil-transmitted helminths (STHs) in anaemia endemicity; and (ii) develop a high resolution predictive risk map of anaemia for the municipality of Dande in northern Angola. We used parasitological survey data for children aged ≤15 years to build Bayesian geostatistical models of malaria (PfPR≤15), S. haematobium, Ascaris lumbricoides and Trichuris trichiura and predict small-scale spatial variations in these infections. Malnutrition, PfPR≤15, and S. haematobium infections were significantly associated with anaemia risk. An estimated 12.5%, 15.6% and 9.8% of anaemia cases could be averted by treating malnutrition, malaria and S. haematobium, respectively. Spatial clusters of high risk of anaemia (>86%) were identified. Using an individual-level approach to anaemia mapping at a small spatial scale, we found that anaemia in children aged ≤15 years is highly heterogeneous and that malnutrition and parasitic infections are important contributors to the spatial variation in anaemia risk. The results presented in this study can help inform the integration of the current provincial malaria control programme with ancillary micronutrient supplementation and control of neglected tropical diseases such as urogenital schistosomiasis and STH infections.

Accurate quantitative assessment of infection with soil transmitted helminths and protozoa is key to the interpretation of epidemiologic studies of these parasites, as well as for monitoring large scale treatment efficacy and effectiveness studies. As morbidity and transmission of helminth infections are directly related to both the prevalence and intensity of infection, there is particular need for improved techniques for assessment of infection intensity for both purposes. The current study aimed to evaluate two multiplex PCR assays to determine prevalence and intensity of intestinal parasite infections, and compare them to standard microscopy.Faecal samples were collected from a total of 680 people, originating from rural communities in Timor-Leste (467 samples) and Cambodia (213 samples). DNA was extracted from stool samples and subject to two multiplex real-time PCR reactions the first targeting: Necator americanus, Ancylostoma spp., Ascaris spp., and Trichuris trichiura; and the second Entamoeba histolytica, Cryptosporidium spp., Giardia. duodenalis, and Strongyloides stercoralis. Samples were also subject to sodium nitrate flotation for identification and quantification of STH eggs, and zinc sulphate centrifugal flotation for detection of protozoan parasites. Higher parasite prevalence was detected by multiplex PCR (hookworms 2.9 times higher, Ascaris 1.2, Giardia 1.6, along with superior polyparasitism detection with this effect magnified as the number of parasites present increased (one: 40.2% vs. 38.1%, two: 30.9% vs. 12.9%, three: 7.6% vs. 0.4%, four: 0.4% vs. 0%). Although, all STH positive samples were low intensity infections by microscopy as defined by WHO guidelines the DNA-load detected by multiplex PCR suggested higher intensity infections.Multiplex PCR, in addition to superior sensitivity, enabled more accurate determination of infection intensity for Ascaris, hookworms and Giardia compared to microscopy, especially in samples exhibiting polyparasitism. The superior performance of multiplex PCR to detect polyparasitism and more accurately determine infection intensity suggests that it is a more appropriate technique for use in epidemiologic studies and for monitoring large-scale intervention trials.

BackgroundMalaria, schistosomiasis and geohelminth infection are linked to maternal and child morbidity and mortality in sub-Saharan Africa. Knowing the prevalence levels of these infections is vital to guide governments towards the implementation of successful and cost-effective disease control initiatives.Methodology/principal findingsA cross-sectional study of 1,237 preschool children (0-5 year olds), 1,142 school-aged children (6-15 year olds) and 960 women (>15 year olds) was conducted to understand the distribution of malnutrition, anemia, malaria, schistosomiasis (intestinal and urinary) and geohelminths in a north-western province of Angola. We used a recent demographic surveillance system (DSS) database to select and recruit suitable households. Malnutrition was common among children (23.3% under-weight, 9.9% wasting and 32.2% stunting), and anemia was found to be a severe public health problem (i.e., >40%). Malaria prevalence was highest among preschool children reaching 20.2%. Micro-hematuria prevalence levels reached 10.0% of preschool children, 16.6% of school-aged children and 21.7% of mothers. Geohelminth infections were common, affecting 22.3% of preschool children, 31.6% of school-aged children and 28.0% of mothers.ConclusionsHere we report prevalence levels of malaria, schistosomiasis and geohelminths; all endemic in this poorly described area where a DSS has been recently established. Furthermore we found evidence that the studied infections are associated with the observed levels of anemia and malnutrition, which can justify the implementation of integrated interventions for the control of these diseases and morbidities.